Two types of enzymes play a role in liver disease and cancer.
Some cancers are caused by loss of enzymes that should keep cell growth in check. On the flip side, some are caused by over-activation of enzymes that enhance cell growth. Yet drugs that inhibit the overactive enzymes have failed to work against liver cancer. In mouse models, researchers at University of California San Diego School of Medicine have discovered a potential reason — counterintuitively, lack of both types of these enzymes can lead to liver disease and cancer. In human liver tumor samples, they also found that deficiencies in these two enzymes, called Shp2 and Pten, are associated with poor prognosis.
The study, published December 13 by Cell Reports, provides a new understanding of how liver cancer develops, a new therapeutic approach and new mouse model for studying the disease.
“When it comes to liver cancer, I think we’ve been making strategic mistakes,” said senior author Gen-Sheng Feng, PhD, professor of pathology and biological sciences at UC San Diego. “In cancer development, we always thought about two distinct families of enzymes — one promotes cancer, one inhibits it. Many drugs have been developed to block the cancer-promoting pathways, but we and others are now finding that many classical pro-cancer proteins are actually inhibitors.”
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